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I am supposed to synthesize tripeptide, $\mathrm{Ala-Asn-Phe}$, using Merrifield peptide synthesis procedure. Accordingly, I have done followings:

  1. Attached protected $\mathrm{Phe}$ as the first amino acid.
  2. Got rid of protecting group ($\mathrm{BOC}$)
  3. Added asparagine with 2 protecting groups - $\mathrm{BOC}$ for $\alpha$-$\ce{NH2}$ group and $\mathrm{FMOC}$ for the $\gamma$-$\ce{NH2}$ group.
  4. Got rid of $\mathrm{BOC}$ and added $\mathrm{Ala}$ protected with $\mathrm{BOC}$.
  5. Got rid of $\mathrm{BOC}$ and $\mathrm{FMOC}$, and used $\ce{HF}$ to release the peptide.

Is this going to work? The thing that worries me the most is the $\gamma$-amino group and using $\mathrm{FMOC}$ - is that a good idea?

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  • $\begingroup$ Are you following a known protocol for solid-state synthesis? My question is because I wonder why you have to protect amide $\ce{NH2}$. Look, when you get asparagine attached to phenylalanine, you got anothe peptide (amide) bond with $\ce{NH}$ bond, but you didn't care to protect that. $\endgroup$ – Mathew Mahindaratne Nov 27 '19 at 0:06
  • $\begingroup$ @MathewMahindaratne well NH from peptide bond will not react with -COOH group of alanine that I am adding next... Or am I mistaken? $\endgroup$ – Geek Nov 27 '19 at 0:29
  • $\begingroup$ My point is it's not necessary to protect amide $\ce{CONH2}$ group. It is not competitive enough with readily available $\alpha$-$\ce{NH2}$ group for DCC coupling. $\endgroup$ – Mathew Mahindaratne Nov 27 '19 at 0:46
  • $\begingroup$ I agree, primary amides are not strong nucleophiles so it is not necessary to protect the Asparagine amide. I presume you are using coupling agents to attach the Asparagine and Alanine $\endgroup$ – Waylander Nov 27 '19 at 8:12
  • $\begingroup$ You just don't need the FMOC at all. $\endgroup$ – Beerhunter Nov 27 '19 at 17:11

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